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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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3 terms
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Biological process
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immune response
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20 terms
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Biochemical function
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receptor binding
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4 terms
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DOI no:
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Biochemistry
41:10418-10425
(2002)
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PubMed id:
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The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions.
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V.Booth,
D.W.Keizer,
M.B.Kamphuis,
I.Clark-Lewis,
B.D.Sykes.
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ABSTRACT
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The structure of IP-10 was solved by NMR spectroscopy and represents the first
structure from the class of agonists toward the receptor CXCR3. CXCR3 binding
chemokines are unique in their ability to bind receptors from both the CC and
CXC classes of chemokine receptors. An unusual structural feature of IP-10 was
identified that may provide the basis for the ability of IP-10 to bind both
CXCR3 and CCR3. The surface of IP-10 that interacts with the N-terminus of CXCR3
was defined by monitoring changes in the NMR spectrum of IP-10 upon addition of
a CXCR3 N-terminal peptide. These studies indicated that the interaction
involves a hydrophobic cleft, formed by the N-loop and 40s-loop region of IP-10,
similar to the interaction surface observed for other chemokines such as IL-8.
An additional region of interaction was observed that consists of a hydrophobic
cleft formed by the N-terminus of IP-10 and 30s-loop of IP-10.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.L.Salanga,
and
T.M.Handel
(2011).
Chemokine oligomerization and interactions with receptors and glycosaminoglycans: the role of structural dynamics in function.
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Exp Cell Res, 317,
590-601.
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B.H.Cheng,
Y.Liu,
X.Xuei,
C.P.Liao,
D.Lu,
M.E.Lasbury,
P.J.Durant,
and
C.H.Lee
(2010).
Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages.
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BMC Microbiol, 10,
103.
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A.Egesten,
A.I.Olin,
H.M.Linge,
M.Yadav,
M.Mörgelin,
A.Karlsson,
and
M.Collin
(2009).
SpeB of Streptococcus pyogenes differentially modulates antibacterial and receptor activating properties of human chemokines.
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PLoS ONE, 4,
e4769.
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A.Ravindran,
P.R.Joseph,
and
K.Rajarathnam
(2009).
Structural basis for differential binding of the interleukin-8 monomer and dimer to the CXCR1 N-domain: role of coupled interactions and dynamics.
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Biochemistry, 48,
8795-8805.
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D.B.Njoku,
Z.Li,
J.L.Mellerson,
R.Sharma,
M.V.Talor,
N.Barat,
and
N.R.Rose
(2009).
IP-10 protects while MIP-2 promotes experimental anesthetic hapten - induced hepatitis.
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J Autoimmun, 32,
52-59.
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F.T.Schulthess,
F.Paroni,
N.S.Sauter,
L.Shu,
P.Ribaux,
L.Haataja,
R.M.Strieter,
J.Oberholzer,
C.C.King,
and
K.Maedler
(2009).
CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling.
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Cell Metab, 9,
125-139.
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J.Hol,
A.M.Küchler,
F.E.Johansen,
B.Dalhus,
G.Haraldsen,
and
I.Oynebråten
(2009).
Molecular requirements for sorting of the chemokine interleukin-8/CXCL8 to endothelial Weibel-Palade bodies.
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J Biol Chem, 284,
23532-23539.
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R.J.Bodnar,
C.C.Yates,
M.E.Rodgers,
X.Du,
and
A.Wells
(2009).
IP-10 induces dissociation of newly formed blood vessels.
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J Cell Sci, 122,
2064-2077.
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T.Loos,
A.Mortier,
M.Gouwy,
I.Ronsse,
W.Put,
J.P.Lenaerts,
J.Van Damme,
and
P.Proost
(2008).
Citrullination of CXCL10 and CXCL11 by peptidylarginine deiminase: a naturally occurring posttranslational modification of chemokines and new dimension of immunoregulation.
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Blood, 112,
2648-2656.
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T.R.Wuest,
and
D.J.Carr
(2008).
Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection.
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J Immunol, 181,
7985-7993.
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H.Fernando,
G.T.Nagle,
and
K.Rajarathnam
(2007).
Thermodynamic characterization of interleukin-8 monomer binding to CXCR1 receptor N-terminal domain.
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FEBS J, 274,
241-251.
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M.R.Yeaman,
N.Y.Yount,
A.J.Waring,
K.D.Gank,
D.Kupferwasser,
R.Wiese,
A.S.Bayer,
and
W.H.Welch
(2007).
Modular determinants of antimicrobial activity in platelet factor-4 family kinocidins.
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Biochim Biophys Acta, 1768,
609-619.
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S.J.Allen,
S.E.Crown,
and
T.M.Handel
(2007).
Chemokine: receptor structure, interactions, and antagonism.
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Annu Rev Immunol, 25,
787-820.
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D.Vergote,
G.S.Butler,
M.Ooms,
J.H.Cox,
C.Silva,
M.D.Hollenberg,
J.H.Jhamandas,
C.M.Overall,
and
C.Power
(2006).
Proteolytic processing of SDF-1alpha reveals a change in receptor specificity mediating HIV-associated neurodegeneration.
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Proc Natl Acad Sci U S A, 103,
19182-19187.
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K.Rajarathnam,
G.N.Prado,
H.Fernando,
I.Clark-Lewis,
and
J.Navarro
(2006).
Probing receptor binding activity of interleukin-8 dimer using a disulfide trap.
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Biochemistry, 45,
7882-7888.
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L.Rajagopalan,
and
K.Rajarathnam
(2006).
Structural basis of chemokine receptor function--a model for binding affinity and ligand selectivity.
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Biosci Rep, 26,
325-339.
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R.A.Colvin,
G.S.Campanella,
L.A.Manice,
and
A.D.Luster
(2006).
CXCR3 requires tyrosine sulfation for ligand binding and a second extracellular loop arginine residue for ligand-induced chemotaxis.
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Mol Cell Biol, 26,
5838-5849.
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V.Booth,
I.Clark-Lewis,
and
B.D.Sykes
(2004).
NMR structure of CXCR3 binding chemokine CXCL11 (ITAC).
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Protein Sci, 13,
2022-2028.
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PDB code:
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V.Petkovic,
C.Moghini,
S.Paoletti,
M.Uguccioni,
and
B.Gerber
(2004).
Eotaxin-3/CCL26 is a natural antagonist for CC chemokine receptors 1 and 5. A human chemokine with a regulatory role.
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J Biol Chem, 279,
23357-23363.
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Y.Kise,
S.W.Lee,
S.G.Park,
S.Fukai,
T.Sengoku,
R.Ishii,
S.Yokoyama,
S.Kim,
and
O.Nureki
(2004).
A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase.
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Nat Struct Mol Biol, 11,
149-156.
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PDB code:
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G.J.Swaminathan,
D.E.Holloway,
R.A.Colvin,
G.K.Campanella,
A.C.Papageorgiou,
A.D.Luster,
and
K.R.Acharya
(2003).
Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine.
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Structure, 11,
521-532.
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PDB codes:
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G.S.Campanella,
E.M.Lee,
J.Sun,
and
A.D.Luster
(2003).
CXCR3 and heparin binding sites of the chemokine IP-10 (CXCL10).
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J Biol Chem, 278,
17066-17074.
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I.Clark-Lewis,
I.Mattioli,
J.H.Gong,
and
P.Loetscher
(2003).
Structure-function relationship between the human chemokine receptor CXCR3 and its ligands.
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J Biol Chem, 278,
289-295.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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